PROJECT SUMMARY Zonulin and Biobehavioral Mechanisms in Oral Inflammatory Diseases The prevalence of chronic inflammatory diseases has increased over the last 50 years. Patients with such diseases are faced with potentially life-long symptoms that affect their overall health and quality of life. Both biological and psychological factors have been demonstrated to affect the inflammatory response of the immune system, including in periodontal disease patients. The oral cavity and the rest of the human digestive system function as primary barriers between an individual and potential toxins or other harmful substances. Zonulin, a protein, disrupts this barrier function in the gut via an increase in the permeability of epithelial and vascular tissues, which induces an inflammatory response that can migrate to other bodily systems. Zonulin has been implicated in a number of chronic inflammatory diseases, yet no studies have examined its effects on oral inflammatory diseases (e.g., periodontal disease). Likewise, there is a dearth of research on the psychological mechanisms of the zonulin pathway. The primary objectives of the proposed research and training plan are to first, add to the understanding of biological and psychological mechanisms that may be contributing to oral disease development via the zonulin pathway which could have implications for new diagnostic methods, and durable, cost-effective interventions. Secondly, the research and training plans are designed to facilitate biological, interdisciplinary, and translational research opportunities that would not be possible to obtain without the fellowship. These objectives will provide a unique and value-added experience to the fellow and expedite the launching of his scientific career to focus on an important-yet-understudied area with a potential high impact for oral health research. The first aim of the research is to examine whether patients with moderate to severe periodontal disease have higher zonulin levels than patients with health gingiva. A second aim is to examine whether zonulin mediates the relation between stress and pro- inflammatory cytokines. Thus, this project is aimed to explore the possibility of psychological mechanisms that alter zonulin levels and thereby affect permeability and potential oral inflammation. These aims will be met by collecting data from patients with a range of periodontal disease severity via blood/saliva samples, validated psychological assessments, and a periodontal examination and to conduct statistical analyses testing for specific associations. Results of the study will aid in developing potential salivary diagnostic tools and specific interventions (e.g., to reduce stress) that could improve the outcome of periodontal disease. The training goals will be reached under the guidance of two expert co-sponsors and a team of consultants by attending a summer research experience in mucosal immunology and periodontics, psychoneuroimmunology, biological research, as well as extra coursework on inflammatory disease processes. Completing the research and training plan will allow the fellow to contribute to and gain expertise in a unique niche of oral health sciences as well as prepare him for future projects and scientific work as a competent researcher.